Increased p53 activity does not accelerate telomere-driven ageing.

Isabel García-Cao; Marta García-Cao; Antonia Tomás-Loba; Juan Martín-Caballero; Juana M Flores; Peter Klatt; María A Blasco; Manuel Serrano

doi:10.1038/sj.embor.7400667

PubMed · 16582880

Increased p53 activity does not accelerate telomere-driven ageing.

Isabel García-Cao·Marta García-Cao·Antonia Tomás-Loba·Juan Martín-Caballero·Juana M Flores·Peter Klatt·María A Blasco·Manuel Serrano

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Abstract

There is a great interest in determining the impact of p53 on ageing and, for this, it is important to discriminate among the known causes of ageing. Telomere loss is a well-established source of age-associated damage, which by itself can recapitulate ageing in mouse models. Here, we have used a genetic approach to interrogate whether p53 contributes to the elimination of telomere-damaged cells and its impact on telomere-driven ageing. We have generated compound mice carrying three functional copies of the p53 gene (super-p53) in a telomerase-deficient background and we have measured the presence of chromosomal abnormalities and DNA damage in several tissues. We have found that the in vivo load of telomere-derived chromosomal damage is significantly decreased in super-p53/telomerase-null mice compared with normal-p53/telomerase-null mice. Interestingly, the presence of extra p53 activity neither accelerates nor delays telomere-driven ageing. From these observations, we conclude that p53 has an active role in eliminating telomere-damaged cells, and we exclude the possibility of an age-promoting effect of p53 on telomere-driven ageing.

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Aging Animals Gene Dosage Kinetics Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Telomerase Telomere Tumor Suppressor Protein p53 Up-Regulation Journal Article Research Support, Non-U.S. Gov't

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Isabel García-Cao, Marta García-Cao, Antonia Tomás-Loba, Juan Martín-Caballero, Juana M Flores, Peter Klatt, María A Blasco, Manuel Serrano. 2006-03-31. Increased p53 activity does not accelerate telomere-driven ageing.. https://doi.org/10.1038/sj.embor.7400667

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